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More intensive low-density lipoprotein lowering is associated with fewer subsequent ischemic strokes
Clinical Question
Does more intensive lowering of low-density lipoprotein levels prevent more strokes than less intensive lowering in adults with a history of ischemic stroke?
Bottom line
In this well-done meta-analysis, patients with more intensive LDL therapy had fewer recurrent strokes and major adverse cardiac events but higher rates of hemorrhagic stroke and new onset diabetes compared with those who received less intensive treatment. Since only one study actually evaluated specific LDL targets, a reasonable approach is to use higher doses of medication or more medications, rather than to pursue LDL targets in high-risk patients who are less concerned about the harms. 1a
Reference
Study design: Meta-analysis (randomized controlled trials)
Funding: Government
Setting: Various (meta-analysis)
Synopsis
These authors searched several databases and registries to identify studies that included patients with a history of transient ischemic attack or stroke who were randomized to more intensive or less intensive therapy (not to higher or lower low-density lipoprotein [LDL] targets). The studies had to be at least 6 months in duration and had to report recurrent stroke rates. The authors ultimately included 11 trials with 20,163 participants (67% were men, average age was 64.9 years, and no racial or socioeconomic data were reported). One of the trials was just plain shoddy and 4 studies did not mask the intervention, but the rest were generally at low risk of bias. Most often, the studies compared drugs (eg, statins, a statin plus ezetimibe, PCSK9 inhibitors plus a statin, etc) against placebo or usual care. Only one study included LDL targets. The rate of recurrent stroke during an average of 4 years of follow-up was lower in the more intensively treated participants (8.1% vs 9.3%; number needed to treat [NNT] for 4 years = 87; 95% CI 52 - 265). Eight of the trials also reported that the rate of major adverse cardiac events was lower in the more intensively treated participants (13.9% vs 16.7%; NNT = 36; 26 - 57). It is unclear if the included studies all used the same components to define this latter outcome. Now, the downside: More participants treated intensively had more frequent hemorrhagic strokes (1.3% vs 0.9%; number needed to treat to harm [NNTH] = 236; 137 - 824) and more frequently developed diabetes (8.5% vs 6.8%; NNTH = 57; 35 - 151). The authors found no difference in cognition or in all-cause or cardiovascular mortality. They also found no evidence for publication bias and no significant heterogeneity in the data.
Reviewer
Henry C. Barry, MD, MS
Professor
Michigan State University
East Lansing, MI
Comments
Intense LDL lowering
Does that apply to elderly people above eighty years of age
LDL lowering
Considering the possible risks--hemorrhagic stroke and diabetes--the benefits of lowering LDL intensively, rather than using targets, remain unclear to me.
LDL lowering in previous stroke
It is important to note that this article only speaks to the benefit if greater ldl lowering in secondary prevention of ischemic stroke. Also the harm needs to be taken into account when presenting this information to such a patient.
Low density LP lowering.
Sloppy study.
Statines et préventions secondaires
L’information est pertinente et le bénéfice est non négligeable et le bénéfice paraît bon vu que traiter 87 personnes sur 4 ans sauve un événement subséquent. Mais il reste que le risque de développer le diabète est vraiment pas négligeable surtout avec un chiffre de 57 personnes a traité sur ce que j’assume être 4 ans pour avoir un cas de plus de diabète.
ischemic strokes
lower LDL levels reduce recurrent cva's